defect in melanocyte development; one of the first genetic disorders for which a pedigree was presented in 1786

Inheritance

autosomal dominant; frequency is about 2.5/105 newborns

Clinics

Phenotype and clinics

congenital patches of white skin and white hair, principally located on the scalp, forehead, chest and abdomen and on the limbs; several patients report lifelong severe constipation; a hierarchical correlation has been elaborated between severe or mild phenotypic traits and the associated KIT mutations; in a few patients with interstitial deletions mental retardation and congenital anomalies have been also described

etiology : defective melanoblasts proliferation, survival and migration from the neural crest during development and defective migration of enteric-plexus ganglion cells from the neural crest to the gut

pathology : white spotting in human piebaldism results from the absence of melanocytes from the nonpigmented patches of skin and from hairbulbs in the white patches of hair; occasionally, individuals lack ganglion cells of the intestinal enteric neural plexus, which like melanoblasts, are derived from the neural crest

Neoplastic risk

an increased risk of epithelioma has been reported

Prognosis

in contrast to vitiligo, piebaldism is both congenital and non-progressive

Cytogenetics

Inborn conditions

a few patients with interstitial deletions of chromosome 4q12-q21.1 have been identified; they are charaterized by multiple congenital anomalies, short stature and mental retardation.

proximal frameshifts (84del1; 249del4); Trp557Term; and missense mutations (Cys136Arg; Ala178Thr; Met318Gly) associated with a mild piebald phenotype, the result of pure haploinsufficiency due to a 50% decrease of KIT-dependent signal transduction

no alteration of this gene has been so far identified in typical patients; at difference with the mouse system, where "steel" mice bearing SCF mutations show the "white spotting" phenotype likewise W mice bearing kit mutations; however, as mutations of KIT could not be detected in a consistent fraction of these patients, involvement of SCF is still an open question.